JP2014515621A - Intraluminal drug applicator and method for treating lesioned blood vessels in the body - Google Patents

Abstract

The stent graft is coupled to the flexible member at or near the distal end of the flexible member and can be structured in both a folded state and an expanded state. The stent graft comprises an expandable stent that is secured to a flexible member. A portion of the expandable stent forms a generally tubular structure in the expanded state. The porous polymer mesh is in circumferential contact with each other around a portion of the stent forming a generally tubular structure. The mesh is expandable with the stent and carries at least one therapeutic agent. When the stent graft is in the expanded state and contacts the treatment site, at least one therapeutic agent is transferred to the treatment site by the contact action between the stent graft and the treatment site. The mesh may form a distal opening and a proximal opening that allow fluid flow through the stent graft when the stent graft is in an expanded state.
[Selection] Figure 5

Description

  The present invention relates to systems and methods for providing treatment to diseased blood vessels in the body, such as, for example, blood vessels, aortic annulus, intestines.

  Atherosclerosis treatment has in the past included balloon angioplasty, stent graft placement, drug elution from stents, and more recently drug delivery from coated balloons. 1-4 illustrate the treatment of atherosclerosis using an angioplasty balloon. FIG. 1 shows a blood vessel 1 with a proximal end 2, a distal end 3, a lumen 4 and a mural thrombus or plaque 5. FIG. 2 shows an angioplasty balloon 10 in a deflated state with a deflated balloon 11 and a proximal tip 12. FIG. 3 shows the balloon 11 in an inflated state, breaking the lime stenosis in the vessel wall and pressing the thrombus or plaque 5 against the vessel wall. FIG. 4 shows the blood vessel 1 with the balloon catheter removed and the plaque pressed against the wall. Note that the diameter 4 of the lumen of FIG. 4 is larger compared to FIG.

  The problem with balloon angioplasty is that about 40% of the treated blood vessels undergo reocclusion as a result of smooth muscle cell proliferation and subsequent stenosis of the vessel lumen. Initially, it was hypothesized that stents would maintain vascular patency by inhibiting lumen collapse. In fact, the restenosis rate improved, but it was found that there was about 33% occlusion in 6 months and still unreasonably high. Later, it was found that this re-occlusion was due to the proliferation of smooth muscle cells in the gaps of the stent in the flow to complete occlusion of the lumen.

  For this reason, the next attempt to control restenosis is to coat the stent with an antiproliferative drug (paclitaxel, rapamycin, or the like) and apply the antiproliferative drug from a suitable carrier coated on the stent strut. It was to release. This technique has significantly reduced the amount of restenosis to an order of magnitude in a year. Later, it was determined that late thrombosis occurred in a small number of patients. The cause of this thrombosis was caused by the drug remaining on the stent when the drug was used up or by the drug from the stent itself. The hypothesis was made that it might have the property of coagulating.

  It was then hypothesized that a stent may not be needed at all if the drug could be released into the vessel wall immediately after angioplasty to prevent smooth muscle proliferation that would result in restenosis. This is particularly interesting in the treatment of peripheral arteries such as the leg, where the stent may inadvertently collapse if the patient crosses his / her leg. This has led researchers to turn their interest in coating balloons with drugs.

There are many problems with coating a balloon with a drug:
The balloon is usually folded in a complex manner on the catheter, making it difficult to reliably coat all surfaces of the balloon;
-The solvent used to coat the balloon may distort the balloon, possibly resulting in poor operability and premature balloon rupture,
The balloon must be inflated for an extended period of time before the drug is effectively transferred to the vessel wall, which can cause ischemia of the tissue and downstream organs That may lead to
There is little room on the surface of the balloon to coat the amount of drug necessary to prevent restenosis,
・ When passing the balloon through the guide catheter or blood vessel, most of the drug may be detached from the balloon before reaching the target point. ・ When the balloon is inflated, the drug may fall off or crack Or problems that may not be released from the balloon in a systematic and predictable manner, thereby leading to unpredictable results and emboli. And these problems prevent accurate dosing at the treatment site.

  Devices have also been proposed that deliver an infusible drug via a fluid delivery lumen to a delivery manifold or porous structure that directly contacts the injected drug with the vessel wall. However, these devices also make it difficult to adjust the dose of drug delivered to the lesion. In addition, since antiproliferative drugs commonly used in this application are not water soluble, large volumes of solvent boluses are required to carry the drug, and most of the solvent is toxic.

  Therefore, there is a need for better methods that deliver drugs to the vessel wall and limit restenosis.

  The application also relates to drug delivery to the heart valve of the lesion. When the leaflets calcify, a common disease state occurs in the heart valves. In many cases, calcification occurs at the top of the commissures and limits the full opening of the leaflets by joining the commissures together. A procedure called valvuloplasty was developed several years ago. It consists of inserting a balloon into the valve and inflating it under high pressure, breaking the calcified commissures and allowing them to open and close as usual. This procedure is performed through a small incision in the foot and the balloon is advanced through the arterial system and into the heart. If successful, the patient's health is restored, avoiding the need for surgery and going home within a few days. However, when a balloon is used, scar tissue is formed, the valve is usually narrowed again within 6 months, and the patient is left in the same state as before the operation.

  The formed scar tissue is due to the proliferation of smooth muscle cells. If anti-proliferative drugs are applied to the aortic annulus when inflated, scar tissue can be minimized. This can be achieved by coating the valvuloplasty balloon with an antiproliferative drug and releasing the drug during valvuloplasty. However, many of the same issues listed above remain in place.

  In addition, valvuloplasty can cause cerebral infarction by allowing thrombi and plaque to detach from the valve area and travel toward the brain. Similarly, during peripheral or coronary angioplasty, there is also the risk of removing the plaque and creating an embolization downstream, thereby causing various additional problems.

  The present invention is directed to a device for delivering a therapeutic agent to a treatment site in a blood vessel, valve, glandular or intestinal tract. The apparatus includes a first elongate flexible member having a distal end. The stent graft is coupled to the flexible member at or near the distal end of the flexible member and can be structured in both a folded state and an expanded state. The stent graft comprises an expandable stent that is secured to a flexible member. A portion of the expandable stent forms a generally tubular structure in the expanded state. The porous polymer mesh is in circumferential contact with each other around a portion of the stent forming a generally tubular structure. The mesh is expandable with the stent and carries at least one therapeutic agent. When the stent graft is in an expanded state and contacts the treatment site, the at least one therapeutic agent is transferred to the treatment site by a contact action between the stent graft and the treatment site.

  In one embodiment, the mesh forms a distal opening and a proximal opening that allow fluid flow through the stent graft when the stent graft is in an expanded state. The therapeutic agent can be selected from the group consisting of antiproliferative drugs, cytostatic drugs and migraine drugs.

  In another embodiment, the first elongate flexible member is a guide wire.

  In yet another embodiment, the first elongate flexible member is a first catheter. The second catheter forms a lumen that receives the first catheter. The first catheter is displaceable longitudinally within the lumen of the second catheter. The stent graft is supported on the distal portion of the first catheter that extends distally beyond the distal end of the second catheter. The stent has a distal end and a proximal end. The distal end of the stent is secured at or near the distal end of the first catheter. The proximal end of the stent is secured to the distal end of the second catheter. The stent graft is configured in an expanded state by bringing the first catheter closer to the second catheter, and the stent graft is configured in a folded state by moving the first catheter away from the second catheter. Is done.

  In yet another embodiment, the first elongate flexible member is a first catheter. A sheath covers the first catheter. The first catheter is displaceable longitudinally within the sheath. The stent graft is supported in a folded state within the distal portion of the sheath and extends distally beyond the distal end of the first catheter. The stent has a distal end and a proximal end. The distal end of the stent is not attached to any structure. The proximal end of the stent is secured to the distal end of the first catheter. The stent graft is configured in an expanded state by bringing the sheath closer to the first catheter, and the stent graft is configured in a folded state by moving the sheath away from the first catheter.

  In these embodiments, the balloon catheter is longitudinally displaceable within the lumen of the first catheter. A balloon is secured to the distal end of the balloon catheter. The balloon can have a first position such that the balloon is expanded and positioned away from the stent graft. The balloon can have a second position such that the balloon is expanded and placed within the stent graft.

  In these embodiments, the device can further comprise a second elongate flexible member having a distal end. A generally tubular porous filter element having an open distal end is deployed from the distal end of the second elongate member. The porous filter element has a folded state and an unfolded state. At least a portion of the filter element is configured to contact the vessel wall in its expanded state and prevent the embolus from flowing into the one or more vessels. The second elongate flexible member and the filter element allow longitudinal displacement of the first elongate flexible member through the interior space of the expanded filter element and away from the filter element. Position the flexible member.

  In one embodiment, the filter element is sized to cover a branch vessel for at least one blood vessel located away from the contact point where the filter element contacts the vessel wall in the expanded state, and the embolus flows into the branch vessel. To prevent it.

  In another embodiment, the filter element has a self-expanding element that self-expands into a shape in which a portion of the porous filter element contacts the vessel wall.

  The filter element can have a closed proximal end that captures the embolus, or an open proximal end that allows the embolus to exit through outflow from the open proximal end.

  The filter element can be configured to contact the wall of the ascending aorta and prevent the embolus from reaching the brain feeding artery.

  In another aspect, a surgical method is provided for delivering at least one therapeutic agent to a treatment site of a valve, glandular or intestinal tract, wherein the method includes the stent graft positioned at the treatment site and in the expanded state in the expanded state. Positioning the device of the present application such that at least one therapeutic agent in contact and thereby carried on the mesh is transferred to the treatment site by contact action between the stent graft and the treatment site.

  In one embodiment, the mesh forms a distal opening and a proximal opening that allow fluid flow through the stent graft when the stent graft is in an expanded state. The at least one therapeutic agent can be selected from the group consisting of antiproliferative drugs, cytostatic drugs and migraine drugs.

  In another embodiment, the balloon can be expanded within an expanded stent graft while the stent graft is in contact with the treatment site. This can help transfer the therapeutic agent carried by the mesh to the treatment site.

  In yet another aspect, a surgical method of delivering at least one therapeutic agent to a treatment site in a blood vessel, valve, glandular or intestinal tract using a stent graft that can be structured in both a folded state and an expanded state Is provided. The stent graft comprises an expandable stent, and a portion of the expandable stent forms a generally tubular structure in the expanded state. The porous polymer mesh is expandable with the stent while in circumferential contact with each other around the stent portion forming the tubular structure. At least one therapeutic agent is carried on the mesh. The stent graft is placed at the treatment site in its expanded state such that when it contacts the treatment site, at least one therapeutic agent is transferred to the treatment site by contact action between the stent graft and the treatment site. The The mesh forms a distal opening and a proximal opening that allow fluid flow through the stent graft when the stent graft is in an expanded state. The at least one therapeutic agent can be selected from the group consisting of antiproliferative drugs, cytostatic drugs and migraine drugs. The balloon can be positioned within the stent graft in an expanded state while the stent graft is in contact with the treatment site to help transfer the therapeutic agent carried by the mesh to the treatment site.

It is the schematic of a diseased blood vessel with restenosis. It is the schematic of the balloon catheter which performs the balloon angioplasty by a prior art. It is the schematic of the balloon catheter which performs the balloon angioplasty by a prior art. 4 is a schematic view of the diseased blood vessel of FIG. 1 after the balloon angioplasty shown in FIGS. 1 shows a first embodiment of a drug delivery device according to the present application. FIG. 1 shows a first embodiment of a drug delivery device according to the present application. FIG. 1 shows a first embodiment of a drug delivery device according to the present application. FIG. FIG. 3 shows a second embodiment of a drug delivery device according to the present application. FIG. 3 shows a second embodiment of a drug delivery device according to the present application. FIG. 10 shows an embodiment of a balloon catheter used in combination with the apparatus of FIGS. 8 and 9. FIG. 10 shows an embodiment of a balloon catheter used in combination with the apparatus of FIGS. 8 and 9. FIG. 10 shows an embodiment of a balloon catheter used in combination with the apparatus of FIGS. 8 and 9. FIG. 6 shows an alternative embodiment of a drug delivery device according to the present application. FIG. 6 shows an alternative embodiment of a drug delivery device according to the present application. 1 is a schematic diagram of a human heart. It is the schematic which simplified the aorta and the left ventricle of the heart. Embodiments of deployment catheter and embolic filter element deployed in the aortic arch and used in combination with the devices of FIGS. 8-12 to provide at least therapeutic agent to the lesioned aortic valve to protect it from emboli entering the cerebral feeding artery FIG. Embodiments of deployment catheter and embolic filter element deployed in the aortic arch and used in combination with the devices of FIGS. 8-12 to provide at least therapeutic agent to the lesioned aortic valve to protect it from emboli entering the cerebral feeding artery FIG. Embodiments of deployment catheter and embolic filter element deployed in the aortic arch and used in combination with the devices of FIGS. 8-12 to provide at least therapeutic agent to the lesioned aortic valve to protect it from emboli entering the cerebral feeding artery FIG. Embodiments of deployment catheter and embolic filter element deployed in the aortic arch and used in combination with the devices of FIGS. 8-12 to provide at least therapeutic agent to the lesioned aortic valve to protect it from emboli entering the cerebral feeding artery FIG. Embodiments of deployment catheter and embolic filter element deployed in the aortic arch and used in combination with the devices of FIGS. 8-12 to provide at least therapeutic agent to the lesioned aortic valve to protect it from emboli entering the cerebral feeding artery FIG. Embodiments of deployment catheter and embolic filter element deployed in the aortic arch and used in combination with the devices of FIGS. 8-12 to provide at least therapeutic agent to the lesioned aortic valve to protect it from emboli entering the cerebral feeding artery FIG. FIG. 23 illustrates an alternative embodiment of the apparatus of FIGS. 8-9 for use in combination with the deployment catheter and embolic filter element of FIGS. 17-22. FIG. 23 illustrates an alternative embodiment of the embolic filter element of FIGS. 17-22. FIG. 3 shows a device deployed in the aortic arch and used to apply at least a therapeutic agent to a diseased aortic valve to protect it from emboli entering the cerebral feeding artery.

  As used herein, the term “distal” is generally defined as the direction of the patient's heart or away from the user of the system / apparatus / device. Conversely, “proximal” generally means in a direction away from the patient's heart or toward the user of the system / apparatus / device.

  Referring to FIGS. 5 and 6, there is shown one embodiment of a drug delivery device 20 according to the present application. The device 20 includes a first catheter 21 that forms a central lumen that can receive and follow a guidewire 22. The second catheter 29 forms a central lumen that receives the first catheter 21 and allows the first catheter 21 to move distally and proximally within the central lumen relative to the second catheter 29. to enable. Both the first catheter 21 and the second catheter 29 are practically flexible so that, in use, they can be manipulated through the tortuous path of the vasculature. A stent graft-like structure 23 (hereinafter referred to as a stent graft 23) is supported by a distal portion of the first catheter 21 that extends beyond the distal end of the second catheter 29. The stent graft 23 includes a polymer mesh 25 secured to (or integrally formed with) an expandable stent 24. Stent 24 includes a network of filaments with an interstitial space between the filaments. The distal end of the stent 24 is secured to the first catheter 21 at a position 27 (at or near the distal end of the first catheter 21). The proximal end of the stent 24 is secured to the second catheter at position 26 (at or near the distal end of the second catheter 29). For the stent 24, a mandrill is first placed inside each catheter, then the stent is placed on the catheter in the attachment target area, and then a temporary heat-shrinkable Teflon tube is placed on the stent. The stent can be fused to the catheter by heating the Teflon tube to the melting point of the catheter material and can be secured to the catheters 29, 21. Forces from heat-shrinkable Teflon and clamshell force the stent filaments into the molten catheter material. The assembly is then cooled and the Teflon tube is removed. In this way, the stent is fixed to the catheter. Other suitable fastening methods can also be used.

  The stent 24 can be expanded from the folded (that is, low posture) state (FIG. 6) to the expanded state (FIG. 5) by moving the first catheter 21 closer to the second catheter 29. Further, by moving the first catheter 21 away from the second catheter 29, the first catheter 21 can be folded from the expanded state (FIG. 5) to the folded state (FIG. 6). The mesh 25 expands and collapses together with the stent 24.

  The mesh 25 can contact the inner surface of the stent 24 with the outer surface of the stent 24 exposed. The mesh 25 can also be in mutual contact with the outer surface of the stent 24 with the inner surface of the stent 24 exposed. The mesh 25 can also be in mutual contact with both the outer and inner surfaces of the stent 24 and cover portions of both the outer and inner surfaces of the stent 24. A radiopaque landmark 28 can be placed at or near the distal end of the second catheter 29 for positioning using fluoroscopy. Similarly, a radiopaque landmark (not shown) may be placed at or near the distal end of the first catheter 21 for positioning using fluoroscopy. One or more radiopaque landmarks (not shown) may be placed in or on the stent 24 to assist in fluoroscopic positioning.

  The expanded stent 24 configuration has frustoconical ends, as shown in FIG. 5, and can form a generally tubular structure (such as a central cylindrical portion, etc.). The mesh 25 can contact the generally tubular structure of the stent 24 while leaving at least a portion of the frustoconical end of the stent 24 open as shown in FIG. In this configuration, the distal and proximal ends of the mesh 25 form a distal opening and a proximal opening, respectively. The blood flows into the stent graft 23 through the open filament at the distal frustoconical end of the stent and the distal opening of the mesh 25, as represented by the arrow 30 in FIG. The proximal opening and the opening filament at the proximal frustoconical end of the stent 24 can flow outward. The folded state of the stent 24 as in FIG. 6 preferably provides the maximum cross-sectional diameter that flows through the stent graft 23, which is less than or equal to the outer diameter of the second catheter 29.

  The mesh 25 is constructed from a porous polymeric material suitable for carrying a therapeutic agent such as, for example, a porous electrostatic spun polyurethane. The mesh 25 preferably has a thickness in the range of 0.1 mm to 0.001 mm, and more preferably has a thickness of 0.01 mm. The therapeutic agent is intact or carried by a carrier (eg, gelatin, albumin, polysaccharide, carbohydrate, dextran, polymer, hydrogel, surface modifier, eg, a polyolefin containing fluorine or silicon, or other suitable carrier). In this state, the porous structure of the mesh 25 may be vacuum impregnated. Alternatively, the therapeutic agent may be mixed with a solution of a material that will eventually be spun into a mesh and spun together with the mesh simultaneously with the formation of the therapeutic agent. The dried mesh thus formed is loaded with a therapeutic agent, and the therapeutic agent is eluted from the mesh when the mesh comes into contact with the blood vessel to be treated. The therapeutic agent is preferably insoluble in water or blood and can be transferred to the tissue by lipophilicity. The porous structure of the mesh 25 allows blood to pass through the mesh 25. A thin film (not shown) may be lined on the inner surface of the stent 24 or the mesh 25 so that the thin film blocks blood flow through the mesh 25. The membrane can also function to prevent the therapeutic agent from passing through the stent 24 or mesh 25 to the blood flowing in the blood vessel.

  The mesh 25 can carry one or more therapeutic agents such as anti-proliferative agents, anti-mitotic agents, anti-migration agents. Examples of such therapeutic agents include mitomycin C, 5-fluorouracil, corticosteroids (most commonly corticosteroids triamcinolone acetonide), modified toxins, methotrexate, adriamycin, radionuclides (eg, by reference thereof) The production of protein kinase inhibitors (including protein kinase C inhibitors staurosporine, diindoloalkaloids and TGF-β), as disclosed in US Pat. No. 4,897,255, which is incorporated herein in its entirety. Functions that are stimulators of activation, including derivatives of tamoxifen and functional equivalents, such as plasmin, heparin, or compounds that can lower or inactivate the levels of lipoprotein Lp or its glycoprotein apolipoprotein Equivalent) Nitrogen-releasing compounds (eg, nitroglycerin) or analogs or functional equivalents thereof, paclitaxel or analogs or functional equivalents thereof (eg, taxotere whose active ingredient is paclitaxel, or the registered trademark “Taxol” Therapeutic agents based on the above), inhibitors of specific enzymes (eg, nuclear enzyme DNA topoisomerase II and DAN polymerase, RNA polymerase, adenine guanyl cyclase, etc.), superoxide dismutase inhibitors, terminal deoxynucleotidyl transferase, reverse transcriptase, Antisense oligonucleotides that suppress cell proliferation, angiogenesis inhibitors (eg, endostatin, angiostatin, squalamine), rapamycin, everolimus, zotarolimus, cerivastatin, and flavopiridol and suramin .

  Other examples of therapeutic agents include: peptides or mimetic inhibitors such as antagonists, agonists, antagonists of cell factors that may cause proliferation of cells or pericytes (e.g., , Cytokines (eg, interleukins such as IL-1)), growth factors (eg, PDGF, TGF-α, β, tumor necrosis factors, smooth muscle- and endothelium-derived growth factors such as endothelin and FGF), There are homing receptors (eg, platelets and leukocytes), and extracellular matrix receptors (eg, integrins).

  Representative examples of therapeutic agents useful in drug categories that address cell proliferation include heparin, triazolopyrimidines (eg, the PDGF antagonist trapidil), lovastatin subfragments, and prostaglandin E1 or I2.

  Some of the numerous additional therapeutic agents suitable for the practice of the present invention are disclosed in US Pat. Nos. 5,733,925 and 6,545,097, both of which are incorporated by reference in their entirety. Are incorporated herein by reference.

  As shown in FIG. 6, a guide catheter or sheath 71 may be provided for positioning the device 20 within the vasculature. The guide catheter 71 forms a central lumen for receiving the second catheter 29 (including the first catheter 21, guide wire 22), and the second catheter 29 (including the first catheter 21, guide wire 22) is central. Allows movement in the distal and proximal directions relative to the guide catheter 71 within the lumen. The guide catheter 71 is flexible so that it can be manipulated through the tortuous path of the vasculature during use. The stent 24 may be smoother than the mesh 25. That is, by placing the mesh 25 on the inner surface of the stent 24 with the outer surface of the stent 24 exposed, the outer surface of the stent 24 can function as a bearing, and when the stent graft 23 is advanced through the guide catheter 71, the stent graft 23 Displacement can be facilitated. Furthermore, by arranging the mesh 25 along the inside of the stent 24, it is possible to minimize the possibility that the therapeutic agent carried by the mesh 25 is erroneously removed by contact with the guide catheter 71. Further, having the stent 24 on the outside (with the mesh 25 on the inside) can dent or scratch the vessel wall, thereby allowing the therapeutic agent carried by the mesh 25 to enter the vessel wall. It can be useful for penetration and transfer, and it can also help to relieve stenosis by cutting specific tissue that may cause stenosis of blood vessels.

  In use, a guide wire 22 is introduced into the vasculature and is manipulated through the vasculature to a treatment site (eg, an atherosclerotic lesion site) or a position near it. A guide catheter 71 is introduced into the vasculature on the guide wire 22 and is operated to the treatment site or a position near the treatment site via the vasculature. The device 20 with the stent graft 23 (first catheter 21 and second catheter 29) in the folded state (FIG. 6) is introduced into the vasculature on the guide wire 22, and the treatment site is passed through the vasculature and the guide catheter 71. , Or its neighboring position. In the folded state of FIG. 6, the first catheter 21 is offset from the distal end of the second catheter 29 so that the maximum cross-sectional diameter of the stent graft 23 decreases as the stent 24 extends. In a preferred embodiment, the maximum cross-sectional diameter of the stent graft 23 in the folded state is smaller than the outer diameter of the second catheter 29 to facilitate operation of the device 20 into place. With the stent graft 23 positioned at or near the treatment site, the stent graft 23 moves to the expanded state by moving the first catheter 21 proximally relative to the second catheter 29 (FIG. 5). As a result, the stent graft 23 contacts the blood vessel wall at the treatment site and the therapeutic agent carried by the mesh 25 of the stent-graft 23 is transferred to the treatment site for treatment purposes.

  FIG. 7 shows the stent graft 23 in place in the vessel such that the stent graft 23 contacts the vessel wall of the treatment site 75 (and the mesh 25 is adjacent to the treatment site 75). When fully deployed, blood is free to move through the open frustoconical ends of the stent 25 (particularly, the gap between the ends of the frustoconical shape of the stent 25 as indicated by the arrow 30). And “perfuses” the distal extremities without causing ischemia.

  The stent graft 23 is that the porous polymer structure of the mesh 25 is filled with a large amount of therapeutic agent, and the mesh 25 prevents the therapeutic agent carried by the mesh 25 from being peeled off or peeled off in the guide catheter 71. And the mesh 25 is effective as a balloon in that it is uniformly deformed in a predictable manner. In addition, due to the openness at the proximal and distal ends of the stent 24, the mesh 25 can be deployed over a long period of time without causing ischemia. This is because blood can pass through the open end of the stent 24 and “perfuse” the distal circulatory system when the stent is expanded to contact the vessel wall. Once the therapeutic agent is eluted from the mesh 25, the stent graft 23 can be removed from the vasculature in the reverse order introduced. Furthermore, the filaments of the stent 24 may be configured to scratch the vessel wall. This also causes the drug to penetrate deeper into the tissue of the vessel wall.

  8 and 9 show another embodiment of a drug delivery device according to the present application. The device 33 comprises a catheter 41 that forms a central lumen that can receive and follow the guidewire 22. The catheter 41 is flexible so that it can be manipulated through the tortuous path of the vasculature when in use. A stent graft-like structure 34 (referred to herein as a “stent graft 34”) is supported at the distal end of the catheter 41 and extends beyond the distal end of the catheter 41. Stent graft 34 includes a polymer mesh 36 secured to (or integrally formed with) an expandable stent 35. The stent 35 includes a filament network having interstitial cavities between filaments. First, place a mandrill inside the catheter, then place a stent on the catheter in the area to be attached, then place a temporary heat-shrink Teflon tube on the stent, and then in a hot clamshell type, a Teflon tube The stent 35 can be fixed to the catheter 41 by heating the catheter to the melting point of the catheter material and fusing the stent to the catheter. Forces from heat-shrinkable Teflon and clamshell force the stent filaments into the molten catheter material. The assembly is then cooled and the Teflon tube is removed. In this way, the stent 35 is fixed to the catheter 41. Other suitable fastening methods can also be used. As shown in FIG. 9, the outer sheath 40 forms a central lumen in which the stent graft 34 (and guide wire 22) is received at a distal portion thereof. The outer sheath 40 is flexible so that it can be manipulated through the tortuous path of the vasculature when in use.

  With the stent graft 34 disposed within the distal portion of the lumen of the outer sheath 40, the stent 35 assumes a folded shape (ie, a low profile) as shown in FIG. Stent graft 34 is deployed from the distal portion of the lumen of outer sheath 40 by approaching outer sheath 40 relative to catheter 41. In this deployed position, the stent 35 can be deployed into an expanded state as shown in FIG. The stent 35 may be self-expanding (or expanded by a balloon or other suitable inflation mechanism). It is also folded from the expanded state (FIG. 8) by returning the stent graft 34 to the distal portion of the lumen of the outer sheath 40 by moving the outer sheath 40 away from the catheter 41. Can be folded into The mesh 36 expands / collapses with the stent 35.

  The mesh 36 can contact the inner surface of the stent 35 with the outer surface of the stent 35 exposed. The mesh 36 can also contact the outer surface of the stent 35 with the inner surface of the stent 35 exposed. The mesh 36 can also be in mutual contact with both the inner and outer surfaces of the stent 35 and cover portions of both the inner and outer surfaces of the stent 35. A radiopaque landmark 38 may be placed at or near the distal end of the catheter 41 for positioning using fluoroscopy. Also, one or more radiopaque landmarks (not shown) may be placed in or on the stent 35 to assist in positioning using fluoroscopy.

  The expanded stent 35 configuration can have a proximal frustoconical end, as shown in FIG. 8, to form a generally tubular structure (ie, a cylindrical portion). The mesh 36 can contact the cylindrical portion of the stent 24 while leaving at least a portion of the proximal frustoconical end of the stent 35 open as shown in FIG. In this configuration, the distal and proximal ends of the mesh 25 form a distal opening and a proximal opening, respectively. Blood enters the stent graft 34 by entering through the distal opening of the mesh 36 and out of the open filament at the proximal opening of the mesh 36 and the proximal frustoconical end of the stent 35. Can flow. The folded shape of the stent 35 provides a maximum cross-sectional diameter that flows through the stent graft 34, which is less than or equal to the outer diameter of the distal portion of the lumen of the outer sheath 40.

  The mesh 36 is constructed from a porous polymeric material suitable for carrying a therapeutic agent, such as a porous electrostatic spun polyurethane. The mesh 36 preferably has a thickness in the range of 0.1 mm to 0.001 mm, and more preferably has a thickness of 0.01 mm. The therapeutic agent is intact or by carrier (eg, gelatin, albumin, polysaccharides, carbohydrates, dextran, polymers, hydrogels, surface modifiers such as polyolefins containing fluorine or silicon, or other suitable carriers). The porous structure of the mesh 36 may be vacuum impregnated while being supported. Alternatively, the therapeutic agent may be mixed with a solution of a material that will eventually be spun into a mesh and spun together with the mesh simultaneously with the formation of the therapeutic agent. The dried mesh thus formed is loaded with a therapeutic agent, but when the mesh comes into contact with a blood vessel to be treated, the therapeutic agent is eluted from the mesh. The therapeutic agent is preferably insoluble in water and blood and can be transferred to the tissue by lipophilicity. The porous structure of the mesh 36 allows blood to pass through the mesh 36. A thin film (not shown) may be lined on the inner surface of the stent 35 or the mesh 36 so that the thin film prevents blood flow through the mesh 36. The thin film can also function to prevent the therapeutic agent from passing through the stent 35 or mesh 36 to the blood flowing in the blood vessel.

  The mesh 36 can carry one or more therapeutic agents as described above with respect to the mesh 25.

  The stent 35 may be smoother than the mesh 36. That is, by placing the mesh 36 on the inner surface of the stent 35 with the outer surface of the stent 35 exposed, the outer surface of the stent 35 can function as a bearing, and the stent graft is deployed from the distal portion of the lumen of the outer sheath 40. In doing so, displacement of the stent graft 34 can be facilitated. Further, positioning the mesh 36 along the inside of the stent 35 minimizes the possibility that therapeutic agents carried by the mesh 36 will be accidentally removed by contact with the distal portion of the outer sheath 40. Can do.

  In use, a guide wire 22 is introduced into the vasculature and is manipulated through the vasculature to a treatment site (eg, an atherosclerotic lesion site) or a position near it. The stent graft 34 is housed in the distal portion of the lumen of the outer sheath (FIG. 9), and the outer sheath 40 and the catheter 41 are manipulated via the vasculature on the guide wire 22 to or near the treatment site. Is done. Stent graft 34 is deployed from the distal portion of the lumen of outer sheath 40 by approaching outer sheath 40 relative to catheter 41. With the stent-graft 34 positioned at or near the treatment site, the stent-graft 34 has been deployed into an expanded state (FIG. 8) so as to contact the vessel wall at the treatment site and carried with the mesh 36 of the stent-graft 34. The therapeutic agent is transferred to the treatment site for therapeutic purposes.

  The lumen of the catheter 41 of FIGS. 8 and 9 can receive a balloon catheter 49 that supports an expandable balloon 50 at its distal end, as shown in FIGS. With the stent graft 34 placed in the lumen of the outer sheath 40, the balloon 50 can be placed away from the outer sheath 40 as shown in FIG. In this configuration, the treatment site is expanded by expanding the balloon 50, and the outer sheath 40 can be easily passed to the expanded treatment site. Once the outer sheath 40 has been advanced to the treatment site, the balloon 50 can be positioned away from the outer sheath 40 and the stent graft 34 can be removed by bringing the outer sheath 40 closer to the catheter 41. The sheath 40 can be deployed from the distal portion of the lumen. This configuration (without blood vessels) is shown in FIG. With the stent graft 34 deployed from the outer sheath 40 and placed at the treatment site, the stent graft 34 expands to an expanded state (FIG. 8) so as to contact the vessel wall at the treatment site, and the stent graft 34 mesh. The therapeutic agent carried by 36 is transferred to the treatment site for therapeutic purposes.

  As shown in FIG. 12, the balloon 50 can be placed inside the stent graft 34 (where the stent graft 34 is in an expanded / expanded state). The balloon 50 can be expanded such that the stent graft 34 expands the balloon 50 and presses the vessel wall at the treatment site. Such expansion can assist in the transfer of the therapeutic agent from the mesh 36 of the stent graft 34 to the treatment site. It should be noted that the stent graft 34 is expanded and brought into contact with the tissue of the blood vessel wall for an additional period, and then the balloon 50 is crushed back into the catheter 41, or the balloon is allowed to flow through the stent graft 34. It should be understood that it can be separated from the stent graft (to the relative position shown in FIG. 11).

  It should also be understood that the stent graft 34 can be manufactured and heat set so that the natural body is in a folded state and the sheath 40 on the catheter 41 is not required. The deflated balloon 50 can be placed in the folded stent graft 34, and the assembly can be placed in the lesion to be treated, not only expanding both the balloon 50 and the stent graft 34 together to dilate the blood vessel, At the same time, the therapeutic agent can be transferred. It is further contemplated that the balloon catheter 49/50 can be used in a similar manner for the device 20 of FIGS.

  FIG. 13 illustrates a further embodiment of the present invention, where the stent graft 34 ′ (stent 35 ′ and mesh 36 ′) is integrally attached to the guidewire 22 at the site 27 ′ and is not a catheter with a stent attached. . The distal end of the stent 35 'supports the' mesh 36 '. The stent may continue to be used with a telescopic device that initially performs angioplasty. The telescopic device may be a balloon catheter with a lumen that can be passed through a 'guide wire 22' with a 'stent 25'. After angioplasty, the telescopic device can be withdrawn (eg, into a delivery catheter) and the stent 25 'is deployed to an expanded state as shown in FIG. In this configuration, the stent graft 34 'contacts the vessel wall at the treatment site and the therapeutic agent carried by the mesh 36' of the stent graft 34 'is transferred to the treatment site for treatment purposes. Alternatively, if the telescopic device does not have a lumen to receive the guide wire 22 'with the stent 25', first withdraw the telescopic device from the patient and then advance the guide wire 22 'with the stent 25' to the treatment position Can do. The stent 25 'can be constructed from a shape memory material so that it is self-expandable when delivered to the treatment site. Such self-expansion can be brought about by stimulation of the expanded memory shape as a result of elasticity or superelasticity or by applying energy such as heat.

  FIG. 14 is yet another embodiment of a drug delivery device according to the present application. Device 59 does not use a stent. The device 59 comprises a cylindrical mesh 60 fixed around the deflated balloon 61. The mesh 60 is composed of a porous polymeric material suitable for carrying a therapeutic agent, such as porous electrospun polyurethane. The therapeutic agent is intact or by carrier (eg, gelatin, albumin, polysaccharides, carbohydrates, dextran, polymers, hydrogels, surface modifiers such as polyolefins containing fluorine or silicon, or other suitable carriers). The porous structure of the mesh 36 may be vacuum impregnated while being supported. Alternatively, the therapeutic agent may be mixed with a solution of a material that will eventually be spun into a mesh and spun together with the mesh simultaneously with the formation of the therapeutic agent. The dried mesh thus formed is loaded with a therapeutic agent, and the therapeutic agent is eluted from the mesh when the mesh comes into contact with the blood vessel to be treated. The therapeutic agent is preferably insoluble in water and blood and can be transferred to the tissue by lipophilicity. As described above for mesh 25, mesh 60 can carry one or more therapeutic agents. When the balloon 61 is inflated, the porous mesh 60 expands therewith and releases the therapeutic agent carried so far. The notch 62 shows the balloon 61 below the mesh 60. The mesh 60 can be attached to the catheter or directly to the balloon 61. Once the therapeutic agent has been dispersed, the mesh 60 is removed from the vasculature along with the balloon 61.

  The stent described in this application can be made of either metal, self-expanding or balloon expandable. Typical metals include nitinol, elgiloy, MP35N, superalloy, and titanium. Typical balloon expandable stents include stainless steel, gold, platinum and tantalum. Stents can also be made from polymers such as PET, nylon, PEEK, PEEKEK, polyimine, polyurethane, polyethylene, polypropylene, etc., as long as they have sufficient memory to self-expand when released from the sheath. is there.

  In another aspect of the application, the drug delivery device of the application can be used to apply one or more therapeutic agents to a diseased heart valve.

  Referring to FIG. 15, the human heart is composed of four chambers: two upper atria (right atrium 123 and left atrium 129) and two lower ventricles (right ventricle 124 and left ventricle 135). The atrium (right atrium 123 and left atrium 129) is a receiving room, and the ventricles (right ventricle 124 and left ventricle 135) are discharge rooms. The blood path through the human heart consists of the pulmonary and systemic circulatory systems. Deoxygenated blood is provided from the body, flows to the right atrium 123 via the superior vena cava 122, and is pumped to the right ventricle 124 via the tricuspid valve 125. Deoxygenated blood in the right ventricle 124 is pumped through the pulmonary valve 127 to the pulmonary artery 126 for supply to the lungs. The lungs pump oxygen into the blood. Oxygenated blood flows from the lungs through the pulmonary vein 128 to the left atrium 129 where the blood is pumped through the mitral valve 130 to the left ventricle 135. The blood into which oxygen has been sent is pumped from the left ventricle 135 through the aortic valves 136 and 137 to the aorta for supply to the body. The aorta distributes oxygenated blood to all parts of the body via the general circulation.

  The aorta can be logically divided into three segments / sections consisting of the ascending aorta, the aortic arch and the descending aorta. The ascending aorta (indicated by the number “134” in FIG. 15) extends between the aortic valve 136/137 and the aortic arch (indicated by the number “133” in FIG. 15). The aortic arch 133 is U-shaped and has an arterial branch that supplies oxygenated blood to the brain. Specifically, the brachiocephalic artery 131, the left common carotid artery 132, and the left subclavian artery branch from the aortic arch 133. In FIG. 15, the left subclavian artery is not numbered, but this is an artery that branches from the aortic arch 33 adjacent to the left common carotid artery 132, and is often fused with the left common carotid artery. It is an artery that can be displayed as one artery, leaving the bow 133. These three arteries are collectively referred to herein as “brain feeding arteries”. The ascending aorta 134 is filled with oxygenated blood by the contraction of the left ventricle 135 pushing the blood past the aortic valve 136/137. The aortic valve has an annulus 136 against which an aortic leaflet 137 is attached. Oxygenated blood climbs the ascending aorta 134 and descends through the aortic arch 133 down the descending aorta (number “138” in FIG. 16) to the kidneys and the lower part of the body. FIG. 16 is a simplified schematic view of the aortic valve and the left ventricle of the heart in addition to the aorta.

  FIGS. 17-22 illustrate another embodiment of a drug delivery device according to the present application. The device is used to deliver one or more therapeutic agents to a cardiac lesioned aortic valve. The device comprises a delivery catheter 140 that forms a central lumen that can receive and follow a guidewire (not shown). Delivery catheter 140 is flexible so that, in use, it can be manipulated through the tortuous path of the vasculature. Filter element 150 is supported at the distal end of support tube 140 within the lumen of delivery catheter 140. The support tube 145 extends proximally within the delivery catheter 140 and is flexible so that it can be manipulated through the tortuous path of the vasculature when in use. The filter element 150 is structurally a tubular porous mesh structure similar to the stent graft described above, but its porosity is large enough to allow blood to pass while moving in the brain feeding artery and staying in the brain. In some cases, it blocks particulate matter such as emboli that can cause cerebral infarction. The filter element 150 can be formed from a porous polymer material such as porous electrospun polyurethane. The effective pore size of the mesh must be in the range of 1-10 microns to prevent larger emboli from reaching the brain.

  The distal portion (such as the distal rim) of the filter element 150 includes a self-expandable structure 151 that self-expands into an expanded state and contacts the wall of the ascending aorta 134 as shown in FIGS. be able to. The self-expanding structure 151 can be realized by one or more types of self-expanding elastic materials such as Nitinol, Ergieroy, MP35N, superalloy, and titanium. It can also be made from polymers such as PET, nylon, PEEK, PEEKEK, polyimine, polyurethane, polyethylene, polypropylene, etc., as long as they have sufficient memory to self-expand when expanded. Alternatively, the filter element 150 may be a self-expanding metal or a polymer braid having a spin coat mesh that covers the braid and reduces its pore size.

  The filter element 150 is loaded into the distal portion of the lumen of the delivery catheter 140 with the self-expanding structure 141 in a folded state. Filter element 150 is deployed from the distal portion of the lumen of delivery catheter 140 by approximating delivery catheter 140 against support tube 145 of filter element 150. Other suitable deployment mechanisms may be used. In the unfolded state, as shown in FIGS. 18 to 22, the self-expanding member 151 of the filter member 150 self-expands to the expanded state. Member 151 can also be folded from an expanded state to a folded state by moving delivery catheter 140 away from support tube 145 and returning filter element 150 into the distal portion of the lumen of delivery catheter 150. it can.

  When the tubular filter element 150 is placed in contact with the wall of the ascending aorta 134, the filter element 150 extends distally beyond at least the brain feeding arteries (1231, 132), and the brain feeding artery is upstream thereof. It is formed so as not to receive an embolus released from the side. Specifically, the distal rim 151 of the filter element 150 contacts the wall of the ascending aorta 134 so that the filter element 150 seals any emboli caused by thrombosis or plaque shedding at the aortic valve treatment site. Preventing passage around the part and preventing entry into the protected bifurcation of the vasculature—the brain feeding artery.

  Delivery catheter 140 and filter element 150 supported therein are used in conjunction with the drug delivery device of FIGS. 8 and 9 to deliver one or more therapeutic agents to the aortic valve.

  Specifically, the filter element 150 is loaded into the distal portion of the lumen of the delivery catheter 140 having the folded self-expanding structure 151 and the deployment catheter 140 is introduced into the vasculature, FIG. As shown, the distal portion is manipulated through the vasculature (possibly through a guide wire not shown) such that it is located in the ascending aorta 134. Filter element 150 is deployed from the distal portion of the lumen of delivery catheter 140 by approximating delivery catheter 140 against the support tube of filter element 150. Other suitable deployment mechanisms may be used. In the expanded state, as shown in FIG. 18, the self-expanding member 151 self-expands into contact with the aortic wall.

  With the stent graft 34 housed in the distal portion of the lumen of the outer sheath (FIG. 9), the outer sheath 40 and catheter 41 are introduced into the delivery catheter 140 and the distal end of the outer sheath 40 is the treatment site or its Guided through the catheter (and support tube 145 in the catheter), possibly in the vicinity (eg, in contact with the leaflet 137 at or near the annulus 136, as shown in FIG. 19). Manipulated over a wire (not shown).

  Stent graft 34 is deployed from the distal portion of the lumen of outer sheath 40 by approaching outer sheath 40 relative to catheter 41. The stent graft 34 is placed at or near the treatment site, and the stent graft 34 is expanded to contact the vessel wall at the treatment site as shown in FIG. 20 and is carried by the mesh 36 of the stent graft 34. The therapeutic agent is transferred to the treatment site for therapeutic purposes.

  The lumen of the catheter 41 can receive a balloon catheter 49 that supports an expandable balloon 50 at its distal end, as shown in FIGS. As shown in FIG. 21, the balloon 50 can be placed inside the stent graft 34 (at this time, the stent graft 34 is in an expanded / expanded state). The balloon 50 can be expanded as shown in FIG. 22 such that the stent graft 34 expands the balloon 50 and presses against the leaflets 137 and the annulus 136 of the aortic valve. Such expansion not only can assist in the transfer of therapeutic agent from the mesh 36 of the stent graft 34 to the treatment site, but at the same time valvuloplasty to separate the fused and calcified leaflets from each other at the commissure. Can assist in the execution of the procedure. In order to allow further transfer of the therapeutic agent, the stent graft 34 is expanded and brought into contact with the tissue of the blood vessel wall for an additional period, and then the balloon 50 is collapsed back into the catheter 41 or the balloon is It should be understood that it can be separated from the stent graft.

  One skilled in the art will appreciate that debris and volatile plaque (emboli) can be removed by procedures performed on the annulus 36 and leaflets 37. The filter element 150 captures the embolus and prevents the embolus from entering the brain feeding artery. In this way, the embolus flows into the filter element 50 and prevents inadvertent cerebral infarction by avoiding inflow into the cerebral feeding artery. Emboli captured by the filter element 150 can be aspirated out of the delivery catheter 140, or can remain in the filter element 150 and removed upon removal of the delivery catheter 140 and filter element 150 from the body at the end of the procedure. Anyway.

  Further, it will be appreciated that the drug delivery device described above with respect to FIGS. 5-7 can be used in conjunction with the delivery catheter 140 and filter element 150 to apply one or more therapeutic agents to a diseased aortic valve. I want.

  FIG. 23 shows another embodiment of the stent graft of the present application. In this embodiment, the mesh 36 ′ of the stent graft 34 covers the proximal frustoconical end of the stent 35. In the present embodiment, the blood flow flowing through the lumen of the stent graft 34 is reduced with the stent graft 134 deployed.

  FIG. 24 shows another embodiment of the catheter 140 that incorporates a larger porosity mesh 160 at its proximal end to allow greater blood flow during the procedure. In this case, blood passes through the lumen of the filter element 150 and flows out through the opened mesh 160. In this embodiment, a particular embolus may flow distally past the mesh 160 and at that distal location the embolus may be disassembled in other ways (eg, when passing through the vasculature or Some emboli can be managed by staying in other parts of the vasculature that are less damaging to the patient than being delivered to the brain.

  FIG. 25 illustrates another embodiment of a drug delivery device according to the present invention. In this embodiment, stent graft 285/280 (equivalent to stent graft 34 described herein) is secured to the distal end of filter element 250 (similar to filter element 150 described herein). Both of these elements are supported within the distal portion of the lumen of delivery catheter 240 (corresponding to catheter 140 described herein). In this embodiment, stent graft 285/280 and filter element 250 are deployed one after another from delivery catheter 240 at the treatment site adjacent to the lesioned aortic valve. Emboli removed from the vicinity of the annulus 36 and leaflets 37 flow through the open structure 285 and can flow into the filter element 250 and bypass the brain feeding artery. The balloon is fed through the catheter 140 and filter element 150 to the inside of the stent graft 280, which is inflated to release the drug carried on the mesh of the stent graft 280 and transferred to the annulus 136 and leaflet 137 of the aortic valve. be able to. The catheter described in FIG. 25 is made using a single, continuous stent with mesh porosity varying along the length of the stent. The pore size of the filtration zone 250 may have a diameter of 5 to 20 microns to allow blood flow to the brain while deflecting the embolus. The porosity of the therapeutic agent delivery mesh 280 may be smaller to provide a material that is dense (0.1-10 microns) in capturing and delivering the therapeutic agent.

  The catheter and similar tubular members described herein are not only for proximal handles that allow the catheter and tubular member to be positioned relative to each other, but to inflate the balloon (if an inflatable balloon is used). A proximal inflation port that supplies a pressurized fluid can be used.

  Thus, several embodiments of devices and methods for delivering an intraluminal drug applicator to a treatment site using an applicator as well as removing the device from the vasculature have been described with reference to the drawings. . Although specific embodiments have been described, the present invention is not intended to be limited thereto. This is because the present invention is as broad in scope as the art will permit and the specification is intended to be read as well. For example, the systems and methods of the present application described above for applying a therapeutic agent to an aortic valve may be used to apply a therapeutic agent to other valves of the heart (eg, tricuspid valve 125 and pulmonary valve 127). Where the system would be placed in the superior vena cava 122 and the mesh containing the therapeutic agent would be placed in that valve. In this embodiment, no filter is used because the lungs are a natural trap of embolism and no filtering is required. The system can also be used within the mitral valve 130 in a configuration where the catheter enters the pulmonary vein 128 and a mesh containing a therapeutic agent is placed on the mitral valve. In this procedure, the filter element is placed in the aortic arch by another catheter that is manipulated from the femoral artery in the groin. The system and method of the present application described above for capturing (or bypassing) emboli can be used with any stenotic artery to prevent volatile plaque from becoming clogged downstream.

  The system and method of the present application described above can also be used in the intestine to deliver chemotherapeutic drugs and actinic radiation to treat colon cancer. Similarly, the present application can be used to treat intestinal infections and other diseases such as irritable bowel syndrome and Crohn's disease. Similarly, these aforementioned catheter systems can be used to treat bronchi, bile ducts, lacrimal ducts, etc., where local delivery of therapeutic agents is effective. Accordingly, one of ordinary skill in the art appreciates that further modifications are possible without departing from the spirit and scope of the claims.

Claims (28)

A device for delivering a therapeutic agent to a treatment site in a blood vessel, valve, gland duct or intestinal tract, the device comprising:
a) a first elongate flexible member having a distal end; and b) an expanded state from being coupled and folded to the flexible member at or near the distal end of the flexible member. A stent graft that can be structured into a stent graft,
i) an expandable stent secured to the flexible member, wherein a portion of the expandable stent forms a generally tubular structure in the expanded state;
ii) a porous polymer mesh that is circumferentially in contact with each other around the portion of the stent and expandable with the stent; and
iii) at least one therapeutic agent carried by the mesh, when the stent graft is in the expanded state and contacts the treatment site, by a contact action between the stent graft and the treatment site At least one therapeutic agent, wherein the at least one therapeutic agent is transferred to the treatment site;
A device comprising:   The device of claim 1, wherein the mesh forms a distal opening and a proximal opening that allow fluid flow through the stent graft when the stent graft is in the expanded state.   2. The device of claim 1, wherein the at least one therapeutic agent is selected from the group consisting of an antiproliferative agent, a cytostatic agent, and a migraine agent.   The apparatus of claim 1, wherein the first elongate flexible member is a guide wire.   The apparatus of claim 1, wherein the first elongate flexible member is a first catheter.   And a second catheter forming a lumen for receiving the first catheter, wherein the first catheter is longitudinally displaceable within the lumen of the second catheter, and the stent graft comprises the 6. The device of claim 5, wherein the device is supported on a distal portion of the first catheter that extends distally beyond the distal end of the second catheter.   The stent has a distal end and a proximal end, the distal end of the stent is fixed at or near the distal end of the first catheter, and the proximal end of the stent is the distal end of the second catheter. The device according to claim 6, wherein the device is fixed to an end.   The stent graft is in the expanded state by bringing the first catheter closer to the second catheter, and the stent graft is folded by moving the first catheter away from the second catheter. 8. The device of claim 7, wherein the device is in a state.   And a sheath covering the first catheter, the sheath allowing the first catheter to be displaced longitudinally within the sheath, wherein the stent graft is folded within a distal portion of the sheath 6. The device of claim 5, wherein the device is supported in a state and extends distally beyond the distal end of the first catheter.   The stent has a distal end and a proximal end, the distal end of the stent is not attached to any structure, and the proximal end of the stent is secured to the distal end of the first catheter The apparatus according to claim 9.   The stent graft is in the expanded state by bringing the sheath closer to the first catheter, and the stent graft is in the folded state by moving the sheath away from the first catheter. The apparatus of claim 10. Furthermore,
A balloon catheter displaceable longitudinally within the lumen of the first catheter and having a distal end; and a balloon fixed to the distal end of the balloon catheter;
6. The apparatus of claim 5, comprising:   13. The device of claim 12, wherein the balloon has a first position such that the balloon is expanded and positioned away from the stent graft.   14. The device of claim 13, wherein the balloon has a second position such that the balloon is expanded and positioned within the stent graft. Furthermore,
c) a second elongate flexible member having a distal end; and d) a generally tubular porous filter element having an open distal end deployed from the distal end of the second elongate member, wherein the porous The quality filter element has a collapsed state and a deployed state, and at least a portion of the filter element contacts the vessel wall in its expanded state to prevent the embolus from flowing into one or more blood vessels. The device of claim 1, wherein the device is formed as follows.   The second elongate flexible member and the filter element are spaced apart from the filter element to allow longitudinal displacement of the first elongate flexible member through the interior space of the filter element in an expanded state. The apparatus of claim 15, wherein the first elongate flexible member is positioned.   The filter element has a size that covers a branch pipe with respect to at least one blood vessel disposed in proximity to a contact point where the filter element comes into contact with a blood vessel wall in an expanded state, and an embolus covers the branch pipe. The device according to claim 15, wherein the device is prevented from flowing into the device.   16. The device of claim 15, wherein the filter element comprises a self-expanding element that self-expands to a state in which a portion of the porous filter element is in contact with the vessel wall.   The apparatus of claim 15, wherein the filter element has a closed proximal end that captures an embolus.   16. The device of claim 15, wherein the filter element has an open proximal end and allows the embolus to escape by outflow from the open proximal end.   16. The device of claim 15, wherein the filter element is configured to contact the wall of the ascending aorta to prevent emboli from reaching the brain feeding artery. A surgical method for delivering at least one therapeutic agent to a treatment site in a blood vessel, valve, glandular or intestinal tract, comprising:
a) providing the device of claim 1; and b) positioning the device of claim 1, wherein the stent graft is positioned at a treatment site in the expanded state, whereby the at least one therapeutic agent. Is transferred to the treatment site by a contact action between the stent graft and the treatment site,
A surgical method characterized by comprising:   The surgical method according to claim 22, wherein the mesh forms a distal opening and a proximal opening that allow fluid flow through the stent graft when the stent graft is in the expanded state. .   The surgical method according to claim 22, wherein the at least one therapeutic agent is selected from the group consisting of an antiproliferative drug, a cytostatic drug, and a migraine drug. Furthermore,
23. The surgical method of claim 22, wherein c) expanding a balloon within the stent graft in an expanded state while the stent graft is in contact with a treatment site. A surgical method for delivering at least one therapeutic agent to a treatment site in a blood vessel, valve, glandular or intestinal tract, comprising:
a) providing a stent graft that can be structured in both a folded state and an expanded state, the stent graft comprising:
i) an expandable stent, wherein a portion of the expandable stent forms a generally tubular structure in the expanded state;
ii) a porous polymer mesh that is circumferentially in contact with each other around the portion of the stent and expandable with the stent; and
iii) at least one therapeutic agent carried on the mesh,
And b) positioning the stent graft in the expanded state at a treatment site, whereby the stent graft contacts the treatment site, thereby causing a contact action between the stent graft and the treatment site. The at least one therapeutic agent is transferred to the treatment site by the mesh and the mesh forms a distal opening and a proximal opening that allow fluid flow through the stent graft when the stent graft is in the expanded state. To do,
A surgical method characterized by comprising:   27. The surgical method according to claim 26, wherein the at least one therapeutic agent is selected from the group consisting of antiproliferative drugs, cytostatic drugs, and migraine drugs. Furthermore,
27. The surgical method of claim 26, wherein c) the balloon is expanded within the stent graft in an expanded state while the stent graft is in contact with a treatment site.

Images